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Frontiers in Neuroscience 2023The olfactory tubercle (OT), which is a component of the olfactory cortex and ventral striatum, has functional domains that play a role in odor-guided motivated...
The olfactory tubercle (OT), which is a component of the olfactory cortex and ventral striatum, has functional domains that play a role in odor-guided motivated behaviors. Learning odor-guided attractive and aversive behavior activates the anteromedial (am) and lateral (l) domains of the OT, respectively. However, the mechanism driving learning-dependent activation of specific OT domains remains unknown. We hypothesized that the neuronal connectivity of OT domains is plastically altered through olfactory experience. To examine the plastic potential of synaptic connections to OT domains, we optogenetically stimulated intracortical inputs from the piriform cortex or sensory inputs from the olfactory bulb to the OT in mice in association with a food reward for attractive learning and electrical foot shock for aversive learning. For both intracortical and sensory connections, axon boutons that terminated in the OT domains were larger in the amOT than in the lOT for mice exhibiting attractive learning and larger in the lOT than in the amOT for mice exhibiting aversive learning. These results indicate that both intracortical and sensory connections to the OT domains have learning-dependent plastic potential, suggesting that this plasticity underlies learning-dependent activation of specific OT domains and the acquisition of appropriate motivated behaviors.
PubMed: 37680965
DOI: 10.3389/fnins.2023.1247375 -
Pathological features and molecular signatures of early olfactory dysfunction in 3xTg-AD model mice.CNS Neuroscience & Therapeutics Feb 2024Olfactory dysfunction is known to be an early manifestation of Alzheimer's disease (AD). However, the underlying mechanism, particularly the specific molecular events...
BACKGROUND
Olfactory dysfunction is known to be an early manifestation of Alzheimer's disease (AD). However, the underlying mechanism, particularly the specific molecular events that occur during the early stages of olfactory disorders, remains unclear.
METHODS
In this study, we utilized transcriptomic sequencing, bioinformatics analysis, and biochemical detection to investigate the specific pathological and molecular characteristics of the olfactory bulb (OB) in 4-month-old male triple transgenic 3xTg-AD mice (PS1M146V/APPSwe/TauP301L).
RESULTS
Initially, during the early stages of olfactory impairment, no significant learning and memory deficits were observed. Correspondingly, we observed significant accumulation of amyloid-beta (Aβ) and Tau pathology specifically in the OB, but not in the hippocampus. In addition, significant axonal morphological defects were detected in the olfactory bulb, cortex, and hippocampal brain regions of 3xTg-AD mice. Transcriptomic analysis revealed a significant increase in the expression of neuroinflammation-related genes, accompanied by a significant decrease in neuronal activity-related genes in the OB. Moreover, immunofluorescence and immunoblotting demonstrated an activation of glial cell biomarkers Iba1 and GFAP, along with a reduction in the expression levels of neuronal activity-related molecules Nr4a2 and FosB, as well as olfaction-related marker OMP.
CONCLUSION
In sum, the early accumulation of Aβ and Tau pathology induces neuroinflammation, which subsequently leads to a decrease in neuronal activity within the OB, causing axonal transport deficits that contribute to olfactory disorders. Nr4a2 and FosB appear to be promising targets for intervention aimed at improving early olfactory impairment in AD.
Topics: Mice; Animals; Male; Alzheimer Disease; Smell; Neuroinflammatory Diseases; Amyloid beta-Peptides; Mice, Transgenic; Olfaction Disorders; Disease Models, Animal; tau Proteins
PubMed: 38366763
DOI: 10.1111/cns.14632 -
Learning & Memory (Cold Spring Harbor,... May 2024In this review, we aggregated the different types of learning and memory paradigms developed in adult and attempted to assess the similarities and differences in the... (Review)
Review
In this review, we aggregated the different types of learning and memory paradigms developed in adult and attempted to assess the similarities and differences in the neural mechanisms supporting diverse types of memory. The simplest association memory assays are conditioning paradigms (olfactory, visual, and gustatory). A great deal of work has been done on these memories, revealing hundreds of genes and neural circuits supporting this memory. Variations of conditioning assays (reversal learning, trace conditioning, latent inhibition, and extinction) also reveal interesting memory mechanisms, whereas mechanisms supporting spatial memory (thermal maze, orientation memory, and heat box) and the conditioned suppression of innate behaviors (phototaxis, negative geotaxis, anemotaxis, and locomotion) remain largely unexplored. In recent years, there has been an increased interest in multisensory and multicomponent memories (context-dependent and cross-modal memory) and higher-order memory (sensory preconditioning and second-order conditioning). Some of this work has revealed how the intricate mushroom body (MB) neural circuitry can support more complex memories. Finally, the most complex memories are arguably those involving social memory: courtship conditioning and social learning (mate-copying and egg-laying behaviors). Currently, very little is known about the mechanisms supporting social memories. Overall, the MBs are important for association memories of multiple sensory modalities and multisensory integration, whereas the central complex is important for place, orientation, and navigation memories. Interestingly, several different types of memory appear to use similar or variants of the olfactory conditioning neural circuitry, which are repurposed in different ways.
Topics: Animals; Memory; Drosophila; Mushroom Bodies; Behavior, Animal
PubMed: 38862165
DOI: 10.1101/lm.053810.123 -
ELife Jun 2023The ability to associate reward-predicting stimuli with adaptive behavior is frequently attributed to the prefrontal cortex, but the stimulus-specificity, spatial...
The ability to associate reward-predicting stimuli with adaptive behavior is frequently attributed to the prefrontal cortex, but the stimulus-specificity, spatial distribution, and stability of prefrontal cue-reward associations are unresolved. We trained head-fixed mice on an olfactory Pavlovian conditioning task and measured the coding properties of individual neurons across space (prefrontal, olfactory, and motor cortices) and time (multiple days). Neurons encoding cues or licks were most common in the olfactory and motor cortex, respectively. By quantifying the responses of cue-encoding neurons to six cues with varying probabilities of reward, we unexpectedly found value coding in all regions we sampled, with some enrichment in the prefrontal cortex. We further found that prefrontal cue and lick codes were preserved across days. Our results demonstrate that individual prefrontal neurons stably encode components of cue-reward learning within a larger spatial gradient of coding properties.
Topics: Animals; Mice; Cues; Learning; Adaptation, Psychological; Conditioning, Classical; Reward
PubMed: 37382590
DOI: 10.7554/eLife.84604 -
Cell Reports Aug 2023Long-term memory (LTM) requires learning-induced synthesis of new proteins allocated to specific neurons and synapses in a neural circuit. Not all learned information,...
Long-term memory (LTM) requires learning-induced synthesis of new proteins allocated to specific neurons and synapses in a neural circuit. Not all learned information, however, becomes permanent memory. How the brain gates relevant information into LTM remains unclear. In Drosophila adults, weak learning after a single training session in an olfactory aversive task typically does not induce protein-synthesis-dependent LTM. Instead, strong learning after multiple spaced training sessions is required. Here, we report that pre-synaptic active-zone protein synthesis and cholinergic signaling from the early α/β subset of mushroom body (MB) neurons produce a downstream inhibitory effect on LTM formation. When we eliminated inhibitory signaling from these neurons, weak learning was then sufficient to form LTM. This bidirectional circuit mechanism modulates the transition between distinct memory phase functions in different subpopulations of MB neurons in the olfactory memory circuit.
PubMed: 37590142
DOI: 10.1016/j.celrep.2023.112974 -
ELife Sep 2023We still face fundamental gaps in understanding how molecular plastic changes of synapses intersect with circuit operation to define behavioral states. Here, we show...
We still face fundamental gaps in understanding how molecular plastic changes of synapses intersect with circuit operation to define behavioral states. Here, we show that an antagonism between two conserved regulatory proteins, Spinophilin (Spn) and Syd-1, controls presynaptic long-term plasticity and the maintenance of olfactory memories in . While mutants could not trigger nanoscopic active zone remodeling under homeostatic challenge and failed to stably potentiate neurotransmitter release, concomitant reduction of Syd-1 rescued all these deficits. The Spn/Syd-1 antagonism converged on active zone close F-actin, and genetic or acute pharmacological depolymerization of F-actin rescued the deficits by allowing access to synaptic vesicle release sites. Within the intrinsic mushroom body neurons, the Spn/Syd-1 antagonism specifically controlled olfactory memory stabilization but not initial learning. Thus, this evolutionarily conserved protein complex controls behaviorally relevant presynaptic long-term plasticity, also observed in the mammalian brain but still enigmatic concerning its molecular mechanisms and behavioral relevance.
PubMed: 37767892
DOI: 10.7554/eLife.86084 -
Journal of the Royal Society, Interface Nov 2023Artificial intelligence (AI) and machine learning (ML) present revolutionary opportunities to enhance our understanding of animal behaviour and conservation strategies.... (Review)
Review
Artificial intelligence (AI) and machine learning (ML) present revolutionary opportunities to enhance our understanding of animal behaviour and conservation strategies. Using elephants, a crucial species in Africa and Asia's protected areas, as our focal point, we delve into the role of AI and ML in their conservation. Given the increasing amounts of data gathered from a variety of sensors like cameras, microphones, geophones, drones and satellites, the challenge lies in managing and interpreting this vast data. New AI and ML techniques offer solutions to streamline this process, helping us extract vital information that might otherwise be overlooked. This paper focuses on the different AI-driven monitoring methods and their potential for improving elephant conservation. Collaborative efforts between AI experts and ecological researchers are essential in leveraging these innovative technologies for enhanced wildlife conservation, setting a precedent for numerous other species.
Topics: Animals; Elephants; Artificial Intelligence; Conservation of Natural Resources; Animals, Wild
PubMed: 37963556
DOI: 10.1098/rsif.2023.0367 -
ELife Sep 2023Tastes typically evoke innate behavioral responses that can be broadly categorized as acceptance or rejection. However, research in indicates that taste responses also...
Tastes typically evoke innate behavioral responses that can be broadly categorized as acceptance or rejection. However, research in indicates that taste responses also exhibit plasticity through experience-dependent changes in mushroom body circuits. In this study, we develop a novel taste learning paradigm using closed-loop optogenetics. We find that appetitive and aversive taste memories can be formed by pairing gustatory stimuli with optogenetic activation of sensory neurons or dopaminergic neurons encoding reward or punishment. As with olfactory memories, distinct dopaminergic subpopulations drive the parallel formation of short- and long-term appetitive memories. Long-term memories are protein synthesis-dependent and have energetic requirements that are satisfied by a variety of caloric food sources or by direct stimulation of MB-MP1 dopaminergic neurons. Our paradigm affords new opportunities to probe plasticity mechanisms within the taste system and understand the extent to which taste responses depend on experience.
PubMed: 37750673
DOI: 10.7554/eLife.81535 -
Frontiers in Neural Circuits 2024In the mouse olfactory system, odor information is converted to a topographic map of activated glomeruli in the olfactory bulb (OB). Although the arrangement of... (Review)
Review
In the mouse olfactory system, odor information is converted to a topographic map of activated glomeruli in the olfactory bulb (OB). Although the arrangement of glomeruli is genetically determined, the glomerular structure is plastic and can be modified by environmental stimuli. If the pups are exposed to a particular odorant, responding glomeruli become larger recruiting the dendrites of connecting projection neurons and interneurons. This imprinting not only increases the sensitivity to the exposed odor, but also imposes the positive quality on imprinted memory. External odor information represented as an odor map in the OB is transmitted to the olfactory cortex (OC) and amygdala for decision making to elicit emotional and behavioral outputs using two distinct neural pathways, innate and learned. Innate olfactory circuits start to work right after birth, whereas learned circuits become functional later on. In this paper, the recent progress will be summarized in the study of olfactory circuit formation and odor perception in mice. We will also propose new hypotheses on the timing and gating of olfactory circuit activity in relation to the respiration cycle.
Topics: Animals; Mice; Sensation; Smell; Odorants; Amygdala; Perception
PubMed: 38434487
DOI: 10.3389/fncir.2024.1342576 -
Biomimetics (Basel, Switzerland) Jun 2023We propose a new model for a neuromorphic olfactory analyzer based on memristive synapses. The model comprises a layer of receptive neurons that perceive various odors...
We propose a new model for a neuromorphic olfactory analyzer based on memristive synapses. The model comprises a layer of receptive neurons that perceive various odors and a layer of "decoder" neurons that recognize these odors. It is demonstrated that connecting these layers with memristive synapses enables the training of the "decoder" layer to recognize two types of odorants of varying concentrations. In the absence of such synapses, the layer of "decoder" neurons does not exhibit specificity in recognizing odorants. The recognition of the 'odorant' occurs through the neural activity of a group of decoder neurons that have acquired specificity for the odorant in the learning process. The proposed phenomenological model showcases the potential use of a memristive synapse in practical odorant recognition applications.
PubMed: 37504165
DOI: 10.3390/biomimetics8030277